EP0986951B1 - Dispositif capteur de mouvement permettant de réaliser des tests sur des animaux librement en mouvement - Google Patents

Dispositif capteur de mouvement permettant de réaliser des tests sur des animaux librement en mouvement Download PDF

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Publication number
EP0986951B1
EP0986951B1 EP99307384A EP99307384A EP0986951B1 EP 0986951 B1 EP0986951 B1 EP 0986951B1 EP 99307384 A EP99307384 A EP 99307384A EP 99307384 A EP99307384 A EP 99307384A EP 0986951 B1 EP0986951 B1 EP 0986951B1
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EP
European Patent Office
Prior art keywords
fluid
animal
tube
control means
container
Prior art date
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Expired - Lifetime
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EP99307384A
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German (de)
English (en)
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EP0986951A2 (fr
EP0986951A3 (fr
Inventor
Candice B. Kissinger
William J. Schmidt
Donnie A. Evans
Scott R. Peters
James M. Hampsch
Curtis E. Bohs
W. Gamini Gunaratna
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Inotiv Inc
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Bioanalytical Systems Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/103—Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/11—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb
    • A61B5/1104—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb induced by stimuli or drugs
    • A61B5/1105—Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb induced by stimuli or drugs of laboratory animals, e.g. activity
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K1/00—Housing animals; Equipment therefor
    • A01K1/02—Pigsties; Dog-kennels; Rabbit-hutches or the like
    • A01K1/03—Housing for domestic or laboratory animals
    • A01K1/031—Cages for laboratory animals; Cages for measuring metabolism of animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K23/00—Manure or urine pouches
    • A01K23/005—Manure or urine collecting devices used independently from the animal, i.e. not worn by the animal but operated by a person
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K29/00—Other apparatus for animal husbandry
    • A01K29/005—Monitoring or measuring activity, e.g. detecting heat or mating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0038—Devices for taking faeces samples; Faecal examination devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/007—Devices for taking samples of body liquids for taking urine samples
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150015—Source of blood
    • A61B5/15003—Source of blood for venous or arterial blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150221—Valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150229—Pumps for assisting the blood sampling
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150236—Pistons, i.e. cylindrical bodies that sit inside the syringe barrel, typically with an air tight seal, and slide in the barrel to create a vacuum or to expel blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150206—Construction or design features not otherwise provided for; manufacturing or production; packages; sterilisation of piercing element, piercing device or sampling device
    • A61B5/150244—Rods for actuating or driving the piston, i.e. the cylindrical body that sits inside the syringe barrel, typically with an air tight seal, and slides in the barrel to create a vacuum or to expel blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150992—Blood sampling from a fluid line external to a patient, such as a catheter line, combined with an infusion line; blood sampling from indwelling needle sets, e.g. sealable ports, luer couplings, valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/153—Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/40—Animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2503/00—Evaluating a particular growth phase or type of persons or animals
    • A61B2503/42—Evaluating a particular growth phase or type of persons or animals for laboratory research
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/22—Arrangements of medical sensors with cables or leads; Connectors or couplings specifically adapted for medical sensors
    • A61B2562/221—Arrangements of sensors with cables or leads, e.g. cable harnesses

Definitions

  • This invention relates to an apparatus for use in biomedical research, and, in particular, to a system for conducting infusions, electrophysiology, ultrafiltration, microdialysis, electrochemistry, pharmacokinetics (PK), drug metabolism, drug distribution, sampling of body fluids (e.g. bile, blood), optical fiber transmission and behavioral monitoring in conscious, freely-moving animals.
  • body fluids e.g. bile, blood
  • the means of connection is typically a length of flexible, hollow, plastic tubing, a flexible wire, or an optical fiber.
  • connection of one or more lines of tubing for conveyance of fluids in such tests involves the use of a liquid swivel, or, for electric or optical leads, the use of a swivel-commutator (such as an electrocannular device).
  • a portion of the lead is connected to the top of the swivel which is mounted on a support above the animal, while an additional portion of the lead is connected from the implant on the animal to the underside of the swivel.
  • Liquid swivels are designed so that the top and bottom half rotate independently and an internal seal connects the two halves.
  • a form of commutator is required.
  • the lead is discontinuous, i.e., it is somehow "split" at the swivel, so that the bottom half of the lead may be required to rotate with respect to the top half of the lead.
  • Liquid swivels are frequently unreliable. Further difficulty in their employment results when there is a need to connect more than one tubing line, as in microdialysis.
  • Multi-channel liquid swivels typically use concentric cannulae with concentric, complex seals separating each channel from the next. The seals wear easily when exposed to salty, physiological solutions. When they leak, cross-channel contamination is a common occurrence.
  • Use of liquid swivels is also difficult when an electric or optical line (lead) is to be connected to the animal, for such an electric or optical lead requires the addition of a commutator to maintain contact with leads attached to the animal.
  • the swivel and commutator can accommodate rotation of the respective leads, the leads, or a portion thereof, can become entangled when the leads rotate with respect to each other.
  • connecting tubing for microdialysis typically has an internal diameter of 0.12 mm.
  • a length of 10 cm of such tubing contains a volume of approx. 1.2 ⁇ L of fluid.
  • a two channel liquid swivel such as the stainless steel model available from Instech Laboratories of Plymouth Meeting, Pennsylvania, has a dead volume of 1.4 ⁇ L for the center channel and 18.5 ⁇ L for the side channel.
  • liquid swivels adds further limitations when the fluid within the system is blood.
  • Use of liquid swivels generally requires the use of heparinized saline as a wash fluid for blood sampling since the swivel in contact with the blood leads to clotting in the absence of heparin. Consequently, blood serum testing is unavailable in a system utilizing a liquid swivel due to the presence of heparin.
  • the injection of heparinized saline into the animal affects the PK behavior of drugs and can lead to increased bleeding in the animal. If a method of blood sampling is used in which the animal is not injected with heparinized saline, there is a risk of dehydration of the animal, consequently, the blood sampling activity is significantly restricted.
  • liquid swivels and commutators also results in additional manufacturing costs and in unwanted repair costs. Because the swivels naturally wear out during the course of normal use, continual repair or replacement of the swivel is required. It is preferred to avoid the use of swivels to avoid the extra expense thereof in manufacture and repair, but to maintain the ability to perform operant and metabolic testing of an animal with test leads connected.
  • Matsumura et al. does disclose a movement-responsive apparatus which permits for rotation of the animal by rotating the floor of the cage housing the animal.
  • multiple fluid lines are passed through the center of a device mounted to a fixed support above a cylindrical chamber.
  • the animal is tethered to this device by the electrical lines.
  • the electrical lines are connected through a slip-ring commutator on the exterior of the device. This type of connection means that the top and bottom half of the device rotated independently, like a swivel.
  • the floor of the cylinder portion of the cage is moved in response to the animal's movement while the walls of the cage are immobile.
  • the apparatus of Matsumura et al. has several shortcomings, however.
  • the invention of Matsumura et al. permits full rotation of the animal through three, or more, complete 360° turns before responding to the animal's movement with counterrotation. This movement can create undesirable twisting and stress on the leads connected to the animal. In addition to the potential for equipment malfunctions, the twisting and stress can cause discomfort to the animal thereby altering the animal's behavior.
  • the apparatus of Matsumura et al . does not track rotational or vertical behavior of the animal -- valuable indicators of neurochemical changes occurring in the animal during testing.
  • Clark et al teaches a method and apparatus for automated microsampling of blood which uses a Gilson Minipuls 3 peristaltic pump to withdraw blood from the animal through a sterile polyethylene catheter. The blood is then transported through nonsterile polyethylene tubing which is connected to the catheter using silastic tubing. Within the length of tubing is positioned a liquid swivel to permit the animal to rotate without twisting the tube. Lee valves are used in conjunction with the peristaltic pump to direct the blood sample to chilled open vials.
  • the Lee valve is representative of a valve system in which the blood is in direct contact with valve components, in which the blood departs from the conducting tube when entering the valve, and in which blood returns to another conducting tube when exiting the valve.
  • the use of polyethylene tubing, a swivel and Lee valves mandates the use of heparinized saline as a wash fluid to reduce the risk of clotting within the tube, the swivel, and the valves.
  • Clark et al. has several shortcomings. For example, the shortcomings associated with use of a swivel as discussed supra apply to Clark et al. . Also, use of a peristaltic pump for control, is a high cost solution, partially due to the added costs for calibration of individual systems. The ability to precisely recreate certain experiments is limited due to volumetric errors associated with peristaltic pumps which deliver a pulsatile flow and are subject to degradation of the peristaltic tubes during use -- a change which also affects flow rate. Additionally, sterile and non-sterile polyethylene tubes and catheters are subject to clotting.
  • a tube or catheter Once a tube or catheter is clogged, it must be removed, a replacement piece of tube or catheter must be cut, measured, and installed, and the system must be recalibrated. Further, silastic tubing connections are known to become loose resulting in leakage and/or clotting. More problems result from having valves in contact with blood. First, the potential for clotting exists. Second, once the valve is in contact with blood it cannot be conveniently re-sterilized. Consequently, the valve must be discarded after a single application. Finally, the use of heparinized saline as a wash fluid creates the risk of introducing heparin into the animal which can result in bleeding and can effect the PK behaviour of drugs. Additionally, the presence of heparin eliminates the possibility of collecting blood serum since clotting is required in order to collect the serum by centrifuging.
  • EP 0 872 179 discloses various embodiments of an apparatus for performing a biomedical test on a freely moving animal.
  • the apparatus avoids tangling, crimping and other damage to leads connected to the animal by rotating the animal's cage in response to rotational movement of the animal.
  • Matsumura et al, Journal of Neuroscience Methods, 57 (1995) 145-149 also discloses a cage for an animal that detects the rotation of the animal. Based upon the animal's rotational movement, the floor of the cage rotates in the opposite direction, thereby releasing any excessive twisting of leads that have been attached to the animal for testing purposes.
  • Another advantage of the present invention is to provide a testing apparatus which does not result in undesirable change in the animal's behavior as results from some of the prior art systems.
  • An additional advantage of the present invention is to accommodate both the rotational and vertical movements of an experimental animal by use of a rotational sensor mounted on a counter-balanced arm and tether assembly which keeps leads out of the animal's reach, and reduces animal stress by minimizing collar tension.
  • This same apparatus can be used to sample other body fluids such as bile which can be removed from the bile duct and replaced with an equivalent volume of bile salts solution.
  • the present invention comprises an apparatus for performing at least one biomedical test on a freely-moving animal comprising:
  • the apparatus comprises a container for housing the animal, a means for rotating the container in response to rotational movement of the animal, and at least one lead for performance of at least one biomedical test on the animal.
  • the apparatus in one embodiment comprises a container upwardly tapered from the bottom surface such that feces and urine are directed by the tapered lower section to the hole in the bottom surface of the container.
  • the rotating means also has a hole which aligns with hole in the bottom surface of the container which allows urine and feces to pass through the rotating means.
  • the container in one embodiment further includes a means for separating the feces from the urine. The means for separating the feces from the urine separates and collects urine and feces to allow for metabolic testing. Additionally, the hole in the bottom surface of the container and the aligned hole in the rotating means may be used to pass a support means for a test mechanism, such as a push bar, into the container for purposes of operant behavior testing of the animal.
  • the rotating means includes a rotational sensing means which in one embodiment includes first and second close-ended, limit detectors and a triggering element having at least a portion thereof capable of activating the limit detectors. Analysis of the rotational movement of the animal is made possible by connecting an analysis means with the apparatus. The analysis means receives input from either the first and second limit detectors or from the rotating means. In either event, the signal is generated as a consequence of animal movement, with this signal providing a history of the rotational behavior of the animal.
  • the apparatus in one embodiment further includes a vertical sensing means which has an activating element responsive to the vertical movements of the animal and a vertical detection element positioned to detect the movement of the activating element.
  • the vertical detection element is generally of the type to be activated by an interruption, reflection, or detection of a light beam, a magnetic field, a radioactive field, or a flow of gas or liquid to produce either analog or digital output.
  • the activating means in one embodiment is the counterbalanced arm which moves in response to the animal's vertical movements.
  • the vertical detection element produces an output indicative of the vertical position of the animal, or indicates the number of times the animal's vertical position passes through a predetermined point or points.
  • the apparatus of the present invention in one embodiment further includes at least one test lead for performance of at least one biomedical test.
  • the lead has a first end for connection to the animal and a second end for connection to a device external to both the animal and the containment system.
  • rotational movement of the animal causes the rotating element of the rotating means to trigger either the first or second limit detectors to thereby result in counter-rotation of the container.
  • the rotating and rotational sensing means are mounted on a lever arm which responds to upward and downward movement of the animal through a counter-balanced weight which pulls the rotating and rotational sensing means, and all associated leads away from the animal (during upward movement) and with the animal (during downward movement).
  • the lead is also connected to the vertical sensing means for activation of the activating element of the vertical sensing means in response to vertical movement of the animal,
  • the AMBS apparatus includes a means for conducting fluid, a means for receiving fluid, a means for moving fluid, fluid control means, and a sample collection control means.
  • the means for conducting fluid is resiliently compressible tubing
  • the means for receiving fluid is a refrigerated fraction collector having sealed vials for receiving blood samples
  • the means for moving fluid comprises a syringe pump
  • the fluid control means comprises pinch valves
  • the sample collection control means comprises a personal computer (PC).
  • PC personal computer
  • Other acceptable sample control means include, but is not limited to, an electronic controller, timer, or other regulating device.
  • the tubing provides communication between three areas, namely, the test animal, the refrigerated fraction collector and the syringe pump, which are connected through a three-way connector such as a "Y" or "T" connector.
  • the pinch valves are located so as to control fluid flow to and from these three areas.
  • the pinch valves associated with the tubing which connects the test animal and the refrigerated fraction collector may be combined within a common housing and utilize a common pinch bar so as to realize a three-way pinch valve which operates such that whenever one selected tube is open, the other is shut.
  • the test lead, tubing, and "T" connector have an anticoagulant coating. Since all surfaces in contact with the blood sample are coated, non-heparinized saline solution, which is sterile or not sterile, may be used as a wash fluid to flush the system and to move blood samples within the apparatus.
  • the PC coordinates the pinch valve positions, fraction collector, and syringe activity so as to flush the system, withdraw a blood sample from the animal, move that blood sample to the refrigerated fraction collector, advance the fraction collector to the next vial position or waste, and inject back into the animal any non-used blood as well as an amount of saline equal to the blood sample taken.
  • the PC can also effect the refilling of the syringe pump with sterile saline solution from a sterile saline solution supply means.
  • the present invention offers a simple and reliable means of connecting a device implanted in or attached to an animal to an external controlling or monitoring device located at a distance from the animal which permits the animal to move freely during such biomedical testing.
  • movement-responsive test system 10 is capable of performing biomedical tests on animal 12, which in this embodiment is a laboratory rat.
  • Animal 12 is housed within cage or bowl 14 during performance of the biomedical test(s).
  • Cage 14 is more thoroughly described in association with Fig. 2 , Fig. 4 , Fig. 6 , Fig. 7 , and Fig. 10 hereof, and is connected to powered turntable 16 as is described in association with Fig. 3 hereof.
  • Figures 6 and 7 are in accordance with the present claimed invention.
  • Animal 12 is connected to test leads 18, 20, 22, and 24 and to tether line 26 as is described in greater detail herein.
  • system 10 The primary objective of system 10 is to provide an apparatus which is responsive to the rotational movement of animal 12 during biomedical testing. More specifically, if animal 12 rotates in the direction indicated by animal movement arrow 28, system 10 causes turntable 16 and cage 14 to rotate in the direction indicated by cage movement arrow 30. Similarly, if animal 12 were to rotate in a direction opposite that of animal movement arrow 28, system 10 causes turntable 16 and cage 14 to rotate opposite the direction indicated by cage movement arrow 30. In other words, system 10 causes cage 14 to rotate in the counter-rotation direction of the detected direction of rotation of animal 12. In this manner, test leads 18, 20, 22 and 24 and tether line 26 do not become twisted or entangled upon rotation of animal 12.
  • system 10 includes a means for rotating cage 14 in response to rotational movement of the animal, including sensor assembly 32 for sensing movement of the animal, a means for driving rotation of cage 14 in the appropriate counter-rotational direction (see motor 34 on Fig. 3 , Fig. 4 , and Fig. 5 ), and tether line 26 for connecting animal 12 to sensor assembly 32.
  • Sensor assembly 32 is positioned and suspended above animal 12 in cage 14 by a support means comprising support table 36 having counterbalanced arm 38 pivotally mounted thereon.
  • counterbalanced arm 38 is desirable to take up slack in and to keep leads 18, 20, 22, and 24 and tether line 26 out of the animal's reach and yet allow the animal flexibility of vertical movement without placing unwanted stress on leads 18, 20, 22, and 24 or tether line 26.
  • first lead 18, second lead 20, and third lead 22 all comprise fluid tubing implanted in the head of animal 12 at one end.
  • the other ends of first, second and third leads 18, 20, and 22, extend through sensor assembly 32 (see Fig. 4 ) and are connected to first, second and third syringe pumps 40, 42, and 44, respectively, for delivery of fluids to animal 12.
  • Fourth lead 24, also tubing, is also implanted at one end in the head of animal 12, and is connected to electrically-activated injection valve 46 at its other end for collection of fluid from a probe implanted in animal 12. This fluid would subsequently be injected into a liquid chromatography or mass spectrometry system for analysis. It is important to note that each lead 18, 20, 22 and 24 may be continuous, i.e., to have no breaks or seals therein.
  • tether line 26 is attached by means of a clamp 45 to animal 12 by collar 47.
  • Collar 47 is essentially a belt which is non-invasively fastened about the neck of animal 12.
  • the other end of tether line 26 is connected to sensor assembly 32 as shown in Fig. 4 .
  • leads which comprise electric lines for the receipt or transmission of electric signals, and the optic fibers for the receipt or transmission of light signals. Such lines are illustrated in the bundle shown in Fig. 4 .
  • tether line 26 may be a wire, spring, cable and the like and be within the scope of the invention.
  • cage 14 is essentially a container which restricts the animal's movement during test. Platforms or other enclosures are envisioned to be within the scope of the invention.
  • Fig. 3 shows two sides of one embodiment of a described but unclaimed cage, both disassembled and connected to the turntable and the electric motor for driving the turntable as well as a described but unclaimed cage cover.
  • Bowl 14 rests on turntable 16 as illustrated.
  • bowl 14 is a round bottom bowl, and may be comprised of translucent material, such as plexiglass.
  • affixed, such as by glue, to the bottom exterior surface of bowl 14 is ring or bowl base 15.
  • Bowl base 15 may also be comprised of a material such as plexiglass.
  • Rotatable turntable 16 is placed on, and rotates with respect to, surface 48.
  • plate 17 is attached to turntable 16.
  • Plate 17 is sized to contact the interior circumference surface of bowl base 15 and to hold bowl 14 in place.
  • Drive wheel 52 of motor 34 engages turntable 16 to cause turntable 16, plate 17, bowl base 15, and cage 14 to rotate simultaneously.
  • motor 34 may be any reversible 12-volt DC motor, for example, and turntable 16 may be any suitably sized turntable ranging from the types used in phonographs to the types used for household kitchen cabinets.
  • rotation of the entire cage 14 is advantageous over an arrangement in which only the floor of the cage rotates. Rotating the cage and its contents at the same time as the animal makes this arrangement less disturbing to the animal as it would not appear to the animal that its food and water dispensers are rotating away from the animal as would be caused by rotation of only the cage floor.
  • water and food attached to the walls of cage 14 also rotate.
  • the animal is not likely to learn behavior to compensate for the rotation of the floor only as in the prior art. It is undesirable to modify the animal's behavior during testing.
  • a more stable environment is created for animal 12 and the possibility that bedding or other materials in cage 14 or animal 12 itself will become caught between portions of a cage that rotate and portions that do not rotate is eliminated.
  • cage 14 of this embodiment comprises a round-bottom bowl made of translucent or transparent material such as plastic, plexiglass, or glass.
  • the shape of bowl 14 prevents casual contact between leads 18, 20, 22 and 24 and tether line 26 and the interior walls of bowl 14.
  • the use of such materials permits an observer to view animal 12 while animal 12 is in cage 14 or inserted into or removed from cage 14. It may be desirable, however, for some biomedical tests, to cover cage 14 to reduce the sensation of movement experienced by the animal 12 during rotation of cage 14 by eliminating stationary visual cues residing outside cage 14.
  • cage cover 54 is provided for removable connection to cage 14 as shown in Fig. 3 ,
  • Cover 54 is made of a non-translucent, flexible material, such as dark coloured cloth or flexible plastic.
  • Cover 54 is rectangular in shape and is of a length sufficient to cover the top edge 58 of cage 14. Attached near one edge of the length of cover 54 is at least one fastener 60, which in this embodiment comprises a strip of the hooked portion of a VELCRO TM fastener running the entire length of cover 54. Near the opposing edge of cover 54 is a drawstring fastener 62.
  • mating fastener 64 Attached to bowl 14 near its top edge 58 is at least one mating fastener 64, which in this embodiment comprises the loop portion of a VELCRO TM fastener.
  • Mating fastener 64 is positioned for fastening to fastener 60 of cover 54 so that when cover 54 is so fastened to bowl 14, cover 54 substantially covers the entire exterior surface walls 56 of bowl 14 around the entire circumference thereof.
  • drawstring fastener 62 may be drawn and tied.
  • cover 54 may be of a different shape than the rectangular shape shown in Fig. 3 . It is possible, for example, to shape cover 54 so that no drawstring fastener 62 is required.
  • Fig. 4 shows a top view of the embodiment of the apparatus illustrated in Fig. 1 , except that all leads are gathered together in a single bundle. Specifically, leads including fluid tubing, electric lines and optic fibers are bundled together in lead bundle 66. The external devices to which these leads are connected are not illustrated in this Fig. 4 .
  • sensor assembly 32 is connected to counterbalanced arm 38. Counterbalanced arm 38 is pivotably connected to support table 36 at pivot 68, thus permitting sensor assembly 32 to move up and down with respect to cage 14 and turntable 16.
  • this support means for sensor assembly 32 takes up slack in lead bundle 66 and tether line 26, and keeps lead bundle 66 and tether line 26 above and out of reach of animal 12, while permitting animal 12 to move vertically within cage 14 without placing undesired stress on lead bundle 66, tether line 26, or the ends thereof connected to animal 12 or to the external device (such as syringe pumps 40, 42 and 44 and injector 46 shown in Fig. 1 ).
  • Sensor assembly 32 comprises first and second limit detectors in the form of optical sensors 70 and 72, respectively, connected to counterbalancing arm 38.
  • First and second optical sensors are of the type which emanate a light beam in the direction of paths 71 and 73, respectively (see Fig. 4A ), and which are activated upon interruption of the respective light beam.
  • first and second limit detectors 70 and 72 are LED type opto-interrupters, and may be Motorola Corp.'s model no. H21, for example.
  • Sensors 70 and 72 are set at a predetermined angle with respect to each other, the significance of which is discussed later herein. The angle is a rotational measurement between sensors 70 and 72 with respect to the triggering element (second bracket 84) as described below.
  • first and second limit detectors 70 and 72 are close-ended, each having stop 87 and 89, respectively, which are discussed in greater detail herein in association with Fig. 4A .
  • Sensor assembly 32 also comprises hollow tube 78 within ball bearing 80 which is attached to arm 38 to permit hollow tube 78 to rotate while attached to counterbalancing arm 38 and in the same direction as animal 12 rotates, whether clockwise or counterclockwise.
  • Lead bundle 66 passes through hollow tube 78 in the center of ball bearing 80 so that rotation of hollow tube 78 does not result in rotation of lead bundle 66 or the leads within lead bundle 66.
  • the center of rotation of hollow tube 78 is strategically positioned in this embodiment. Specifically, the axis of rotation of hollow tube 78 permits for intersection by second bracket 84 of both light beams of first and second optical sensors 70 and 72 for activation of the respective sensor 70 or 72 as described herein.
  • first bracket 82 Attached at one end of hollow tube 78 is first bracket 82, and attached at the other end of hollow tube 78 is second bracket 84.
  • first and second brackets 82 and 84 and hollow tube 78 all rotate together when a rotational force is applied thereto to cause hollow tube 78 to rotate within ball bearing 80.
  • First bracket 82 is positioned so that no portion thereof triggers either beam emanating from first and second sensors 70 and 72, and, in this embodiment is located below limit detectors 70 and 72.
  • Tether line 26 is connected to first bracket 82 such that rotational movement of animal 12 causes rotation of first bracket 82, hollow tube 78, and second bracket 84.
  • second bracket 84 has a portion thereof which is capable of intersecting light beams emanating from first and second sensors 70 and 72 in paths 71 and 73, respectively.
  • second bracket 84 is a bracket with the first leg of second bracket 84 positioned so as not to intersect light beams of sensors 70 and 72.
  • the axis of rotation of hollow tube 78, first bracket 82 and second bracket 84 extends through the first leg.
  • the second leg has at least a portion thereof capable of intersecting the light beams of sensors 70 and 72 at or near the positions shown in Fig. 4A . In this manner, upon rotation of the second bracket 84, the second leg of second bracket 84 interrupts the light beams emanating from first and second sensors 70 and 72 at various points -- one point for each light beam.
  • first and second sensors 70 and 72 are "close-ended".
  • the second leg of second bracket 84 is stopped by the respective stop means 87 or 89 of sensors 70 or 72 so that second bracket 84 cannot rotate through the U-shaped interior of sensors 70 and 72.
  • first and second sensors 70 and 72 are either activated or deactivated, and when a close-ended limit detector, such as sensors 70 and 72 are activated, it cannot be deactivated except by reversal or cessation of the rotational motion of second bracket 84 (and hence reversal or cessation of the rotational movement of animal 12).
  • a close-ended limit detector is deactivated, it cannot be activated until second bracket 84 is rotated, as by rotation of animal 12, to cause second bracket 84 to trigger the limit detector.
  • opto-interrupter sensors disclosed in this embodiment represents one of many possible “limit detectors” which can be used.
  • the limit detector can be activated by an interruption or reflection of a light beam, a magnetic field, a radioactive field, a flow of air or liquid, or a simple contact with a microswitch, pressure sensitive button, magnet, electrical contact wire, or other mechanism.
  • "triggering elements” other than the rotating element of this embodiment are also contemplated
  • the limit detectors are to be close-ended, and the triggering element must be such that it activates the limit detectors in response to rotational movement of the animal.
  • the triggering element may be rotational, such as second bracket 84, or may be any other mechanism appropriate to activate the limit detector, including but not limited to a linearly moving device.
  • the limit detectors may be limit switches activated by a triggering element which comprises linearly-moving markers strategically located on a lead screw. When triggering element is not rotational, the rotational movement of animal 12 through tether 26 must be connected, by means well known in the art to the non-rotational movement of the triggering element.
  • the sensor also referred to herein as a "limit detector” is close-ended and thus results in simple electronic control as is hereinafter described.
  • a vertical sensing means which, in this embodiment, comprises vertical sensor assembly 101 which is responsive to vertical movement of animal 12.
  • Vertical sensor assembly 101 includes a third limit detector in the form of optical sensor 102 and an activating element which in this embodiment is provided by counterbalanced arm 38.
  • Optical sensor 102 is of the type which emanates a light beam in the direction of path 104 (see Fig. 4 ), and which is activated upon interruption of the light beam.
  • optical sensor 102 is an LED type opto-interrupter, and may be Model No. H21 made by Motorola, for example. Movement of counterbalanced arm 38 through path 104 thus activates optical sensor 102.
  • the embodiment disclosed represents one of many possible detectors which can be used. In addition to the types of detectors mentioned in conjunction with detecting rotational movement (limit detectors), proximity or position detecting devices using similar principles are contemplated.
  • proximity or position detecting devices using similar principles are contemplated.
  • the linearly moving activating element (counterbalanced arm 38) disclosed other forms of activating elements, including but not limited to rotational devices are envisioned.
  • the activating element may form part of counterbalanced arm 38 at pivot 68, and pivot 68 may comprise the sensing device providing output reflective of the rotational position of counterbalanced arm 38 within pivot 68.
  • the electronic components of system 10 includes first, second, and third sensors 70, 72, and 102, analog controller 90, and motor 34. Electric power is supplied to all components through power cord 92 to analog controller 90.
  • Each optical sensor 70, 72, and 102 has four wires extending therefrom and connected to analog controller 90 as illustrated. Two of such wires are used for provision of power, and two of such wires are for the activation signal of applicable sensor 70, 72, and/or 102.
  • Analog controller 90 also includes output leads 94, 96, and 106 for connection to a recorder or computer 108 to track and analyze the direction and duration of rotation and vertical activity of the animal based on which of optical sensors 70, 72, and/or 102 is activated and the frequency and duration of such movements.
  • Analog controller 90 also includes speed control 98 which comprises a potentiometer for varying the power level sent to motor 34 to thereby vary the speed of rotation of motor drive wheel 52.
  • first bracket 82 is caused to rotate by the connection of tether line 26 to animal 12 and first bracket 82.
  • Second bracket 84 is caused to rotate by rotation of hollow tube 78 about its axis of rotation and about lead bundle 66 (or leads 18, 20, 22, and 24 in Fig. 1 ), but without rotating lead bundle 66 (or leads 18, 20, 22, and 24 in Fig. 1 ).
  • Rotation of first bracket 82 also results in rotation of second bracket, or rotating element 84.
  • the portion of rotating element 84 capable of intersecting the light beams of first and second optical sensors 70 and 72 will eventually activate either first sensor 70 or second sensor 72 by interrupting the respective light beam emanating therefrom.
  • first sensor 70 or second sensor 72 results in receipt of a respective activation signal by analog controller 90.
  • Analog controller 90 determines the polarity of the signal to be sent to motor 34 based on whether first sensor 70 or second sensor 72 has been activated.
  • Analog controller 90 then sends the polarity signal, the amplitude of which may be adjusted by speed control 98, to motor 34 to cause motor drive wheel 52 to rotate in the desired direction and at the desired speed.
  • Rotation of motor drive wheel 52 results in rotation of turntable 16 and cage 14 in a direction opposite of the direction of rotation of animal 12.
  • Rotation of container 14 turns animal 12 and tether line 26, and, in turn, first bracket 82, hollow tube 78, and second bracket 84.
  • second bracket 84 exits sensor 70 or 72 (such as by reversal or cessation of the rotation of animal 12), the respective light beam is restored and the signal to controller 90 terminates, thereby shutting down motor 34 and the movement of turntable 16.
  • first sensor 70 or second sensor 72 Activation of first sensor 70 or second sensor 72 by rotating element 84 also causes the respective sensor, first sensor 70 or second sensor 72, to send a signal down its respective output lead 94 or 96 to computer 108.
  • Computer 108 logs the event as an activation.
  • the signal sent by first sensor 70 or second sensor 72 down its respective output lead 94 or 96 to computer 108, terminates.
  • Computer 108 logs this event as a deactivation.
  • software or hardware residing in computer 108 is then utilized to determine the number of activations and the sensor that was activated. Additionally, computer 108 may include a timer to log the time of activation and deactivation.
  • Computer 108 thereby determines the duration of each activation of sensor 70 or 72 by subtracting from the time activation was logged the logged time that activation stopped.
  • the rotational behavior of animal 12 can also be displayed as a time history of activity.
  • rotating element 84 rotates in a clockwise direction to thereby activate first sensor 70.
  • Activation of first sensor 70 results in a motor signal from analog controller 90 having a polarity to cause drive wheel 52 to rotate in a clockwise direction.
  • the attached computer will log the beginning of rotational activity in the counterclockwise direction based on the activation of first sensor 70. Clockwise rotation of drive wheel 52 causes turntable 16 and cage 14 to rotate in a counterclockwise direction.
  • first and second sensors 70 and 72 are positioned at a predetermined angle with respect to each other as measured with respect to rotating element, second bracket 84.
  • the angle illustrated is approximately 314°. It will be appreciated that this angle need not specifically be set at this value, but rather, the angle does impact the sensitivity of the sensor assembly, i.e., adjustment of the angle between first and second sensors 70 and 72 will render the system more or less responsive to rotational movement of animal 12. Specifically, if first and second sensors 70 and 72 are moved closer together (an angle smaller than 314°), rotating element 84 will interrupt the light beams and activate sensor 70 and 72 more frequently thereby increasing the sensitivity of system 10 to rotational movement of animal 12. If sensors 70 and 72 are further apart (an angle larger than 314°), rotating element 84 will activate sensors 70 and 72 less frequently thereby reducing the sensitivity.
  • the limit detectors' predetermined position is measured with respect to the spacing between the activatable portions of the sensor. Still, the sensitivity of the sensing means (combination of the limit detectors and the triggering element) may be adjusted by adjusting the spacing between the limit detectors with the effect of increasing or decreasing the spacing akin to modification of the angle.
  • computer 108 includes a timer to log the time of an event to thereby subtract from the time that an initial event is logged, the time that a subsequent event is logged, to thereby determine the time animal 12 has spent in a vertical position.
  • FIG. 6 there is shown a cross-sectional view of an embodiment in accordance with the claimed invention of system 11 including an operant behavior container.
  • hole 110 is located in bottom surface 111 of bowl 113.
  • Hollow extension 112 is attached to bottom surface 111 of bowl 113 and aligned with hole 110 of bowl 113.
  • Hole 115 is made in bowl base 117
  • hole 119 is made in plate 121
  • hole 123 is made in turntable 16
  • hole 127 is made in support surface 129.
  • Holes 115, 119, 123, and 127 are aligned with each other and are sized such that hollow extension 112 fits within holes 115, 119, 123 and 127.
  • Support surface 129 is included in the embodiment of Fig. 6 and comprises the top portion of table 114 for support of rotating means 125 and bowl 113.
  • push bar 116 which serves as a means for determining operant behavior of animal 12, is placed within bowl 113, with aligned holes 110, 115, 119, 123, and 127 providing an access for supporting means 131 of push bar 116 located within bowl 113 as well as allowing signal wire 118 to be operatively connected to push bar 116.
  • push bar 116 is supported within bowl 113 by supporting means 131.
  • signal wire 118 may be connected to a recording or analytical device.
  • Signal wire 118 may also be operatively connected to syringe pump 40 (see Fig. 1 ) such that when push bar 116 is depressed by animal 12, syringe pump 40 ejects a discreet amount of drug into lead 18 for delivery into animal 12.
  • bowl 113 is only exemplary of the type of container that can be used with system 11.
  • Other containers such as flat bottomed containers, are within the scope of the invention.
  • bowl base 117 and hollow extension 112. while adding some measure of stability to the embodiment disclosed, are not required in order to allow bowl 113 to be used as an operant chamber.
  • the apparatus of the present invention may also be used as a metabolic chamber.
  • the embodiment in accordance with the claimed invention as shown as Fig. 7 shows bowl 113 which comprises a lower portion upwardly tapering from bottom surface 111.
  • stainless steel cap 120 placed within bowl 113 such that any urine or feces excreted by animal 12 will pass over cap 120.
  • Stainless steel is chosen for its resistance to corrosion when exposed to urine as well as its hardness, since animal 12 may have a tendency to gnaw on cap 120.
  • Cap 120 is shown in greater detail in Fig. 8A and Fig. 8B .
  • cap 120 comprises a plurality of urine slots 122 sized such that urine will pass through the urine slots 122 but which does not permit feces from animal 12 to pass through urine slots 122.
  • Urine slots 122 are located around feces hole 124 which is sized such that feces from animal 12 will pass through.
  • Hollow shaft 126 is attached to the lower surface of cap 120. Hollow shaft 126 serves the purpose of directing feces falling through feces hole 124 straight down.
  • Pins 128 located on the lower surface of cap 120 are designed to fit within receptors 133 in bowl 113 (see Fig. 8C ) providing for a more secure attachment of cap 120 to bowl 113.
  • cap 120 disclosed in Fig. 8A and Fig. 8B is circular, but other shapes are within the scope of the present invention.
  • the salient feature of cap 120 is that it is sized to fit within bowl 113 in such a way that feces excreted by animal 12 will pass over the surface of cap 120, and not pass around the outside of cap 120 to hole 110 in the bottom of bowl 113.
  • the shape and orientation of the disclosed embodiment is one of many shapes and orientations which are within the scope of this invention including but not limited to arcing slots following the circular contour of cap 120 and holes sized such that feces will not pass through.
  • cap 120 is, in this embodiment, comprised of stainless steel, the present invention includes within its scope caps made from other materials possessing the desired properties of corrosion resistance and hardness.
  • funnel 132 is attached to hollow shaft 126 of cap 120 such that urine flowing through urine slots 122 is kept on the outer surface of funnel 132 while feces dropping through feces hole 124 stays inside of funnel 132.
  • Collection dish 134 is aligned with hole 110 in bottom surface 111 of bowl 113 for collection of both the urine and feces. The manner in which urine and feces flow and are collected is described in greater detail below.
  • Fig. 9A and Fig. 9B show in greater detail metabolic collection dish 134.
  • Collection dish 134 comprises inner compartment 136 defined by inner wall 138.
  • Outer compartment 140 is defined by inner wall 138 and outer wall 142. When in position as shown in Fig. 7 , inner compartment 136 is located underneath hole 110 in bottom surface 111 of bowl 113 and underneath hollow shaft 126 of cap 120.
  • Inner compartment 136 is sized to be at least as large as hollow shaft 126 but not as large as flared end of funnel 132.
  • Outer compartment 140 is sized such that entire collection dish 134 is larger than funnel 132, and larger than hollow extension 112. While the embodiment of Fig.
  • FIG. 7 shows the flared end of funnel 132 to be larger than hollow extension 112, the scope of the invention includes but is not limited to a hollow cylinder with a slight outward taper at its lower end.
  • the critical feature being the relative size and shape of compartments 136 and 140, hollow shaft 126, and the larger of hollow extension 112 or funnel 132.
  • the combination of size and shape at a given cross-section is referred to as cross-sectional shape.
  • the present invention includes within its scope cap 120 which allows urine to pass underneath cap 120.
  • cap 120 fits within bowl 113 such that urine may pass under cap 120 but feces can not pass under cap 120.
  • the flow path under cap 120 may be used in addition to urine slots 122 or in place of urine slots 122.
  • the separation of urine from feces would occur as follows. As animal 12 passes feces, it is directed toward hole 110 in bottom surface 111 of bowl 113 by gravity. The feces hits the lower portion upwardly tapering from bottom surface 111 of bowl 113 and rolls to the cap 120. The feces does not pass under cap 120 since the gap between cap 120 and bottom surface 111 of bowl 113 is too small. The feces proceeds onto cap 120. The feces continues on to and through feces hole 124. Hollow shaft 126 and funnel 132 guide the feces into inner compartment 136 of collection dish 134.
  • FIG. 10 An alternate embodiment of a metabolic cage is shown in Fig. 10 .
  • means for separating the feces from the urine 146 is external to bowl 143, which in this embodiment comprises a cylindrically-shaped container.
  • animal support means 160 Positioned above bottom surface 164 of bowl 143 is animal support means 160.
  • Animal support means 160 comprises, in this embodiment, a plurality of overlapping members, which comprise apertures of a size to allow feces and urine to pass through.
  • the members may be wire, such as in a wire mesh, or rods, such as in a grid.
  • animal support means 160 which are within the scope of the present invention, which includes but is not limited to, a plurality of substantially parallel members such as rods.
  • Apertures 161, 162, and 163 are formed within bottom surface 164 of bowl 143, turntable 16, and bowl support surface 129, respectively, for receipt of funnel 147 therethrough as illustrated.
  • Funnel 147 rotates with bowl 143 in this embodiment, but is not required to so rotate unless animal support means 160 is attached to funnel 132 instead of the walls of bowl 143.
  • Funnel 147 extends below the underside of bowl support surface 129 and includes hole 145. Hole 145 of funnel 147 is positioned over alternate collection dish 144 as shown. Alternate collection dish 144, which is shown in greater detail in Fig. 11 , collects urine and feces excreted by animal 12 in the manner which is described in further detail herein.
  • Fig. 11 shows a cross-sectional view of means for separating feces and urine 146 and collection dish 144 utilized in the embodiment of Fig. 10 .
  • means for separating feces and urine 146 comprising mesh 148.
  • Mesh 148 is formed into tapered section 150 which descends to lower rim 152.
  • Mesh 148 is of the type that urine will pass through but that feces will not pass through and comprises a stainless steel mesh, or may be made of other materials which resist corrosion.
  • Vertical section 154 of mesh 148 extends upward from lower rim 152 of mesh 148.
  • mesh 148 is positioned within collection dish 144 due to the fact that mesh 148 is formed to have its lower rim 152 and vertical section 154 in frictional contact with the interior of side wall 149 of collection dish 144, and such that apex 156 of mesh 148 is lower than upper rim 158 of collection dish 144, and such that lower rim 152 of mesh 148 is held above bottom surface 151 of collection dish 144.
  • Depression 169 is provided in bottom surface 151 of collection dish 144 to concentrate urine.
  • feces and urine fall through the apertures of animal support means 160, and are then directed by gravity into funnel 147. Feces and urine then roll and flow, respectively, through hole 145 of funnel 147. Passing through hole 145, feces and urine fall past upper rim 158 of collection dish 144. Both feces and urine then hit at or about apex 156 or tapered section 150 of mesh 148. Urine will then pass through mesh 148, and fall into collection dish 144. Urine flows along bottom surface 151 of collection dish 144 to depression 169 where urine is concentrated.
  • Feces being too large to pass through mesh 148, is directed by tapered section 150 of mesh 148 to gully 167 formed at the junction of vertical section 154, and tapered section 150 of mesh 148. While in gully 167, the feces is out of the direct path of any urine which may be later excreted by animal 12.
  • mesh 148 may be comprised of any material or structure which will allow urine therethrough while not permitting feces to pass therethrough, such as, but not limited to, the use of a formed grid or a netting over a form.
  • the method of suspending mesh 148 above bottom surface 151 of collection dish 144 may be a rack or stand as opposed to friction.
  • collection dish 144 may be of the type shown in Fig. 9A and Fig. 9B , with mesh 148 covering inner compartment 136, allowing feces to collect in outer compartment 140.
  • use of funnel 147 is but one embodiment which is within the scope of the present invention.
  • Other embodiments such as bowl 113 (see Fig. 7 ) are within the scope of the present invention.
  • FIG. 12 An apparatus for performing automated micro blood sampling in animals is diagramed in Fig. 12 .
  • animal 12 is placed within movement-responsive system of the type shown in Fig. 1 .
  • Attached to animal 12 is tether 26, and a jugular cannula having sterile heparinized catheter 135 attached thereto for removal ofblood from animal 12.
  • Catheter 135 is connected to lead 180, by utilizing short polymeric tubes which provide a secure connection by sliding over the ends of the two pieces of tubing being connected.
  • Such an additional connector may result in clotting or leaking of blood passing through the connector.
  • test lead 180 comprises, in this embodiment, tubing having an anti-coagulant coating in the inside thereof to resist clotting within test lead 180.
  • Such anti-coagulant coating may be Carmeda® Bioactive Surface (CBAS), available from Carmeda, of Sweden.
  • Test lead 180 is routed through three-way pinch valve 182 to first intersection or "T" 184, where test lead 180 is joined with collector tubing 181 and connector tubing 191.
  • Collector tubing 181 extends from first "T” 184 through three-way pinch valve 182 to refrigerated fraction collector 186.
  • Fraction collector 186 includes sealed vials 188 for receiving blood samples and drain 189, all as is well known in the art.
  • the present invention includes within its scope sample collection means other than refrigerated fraction collectors. It will be obvious to those skilled in the art that for performance of some experiments, the sample collection means will not need a drain, and the saline and sample may be intermixed.
  • Three-way pinch valve 182 through which test lead 180 and collector tubing 181 extend is of a type well known in the art, and may comprise, for example, Model 161P, manufactured by NR Research of Caldwell, New Jersey. Other means for stopping or allowing fluid flow through tubes 181 and 180 will be obvious to those skilled in the art and are considered to be within the scope of the present invention.
  • test lead 180 or collector tubing 181 is open with the other closed.
  • Test lead 180 and collector tubing 181 cannot both be open or both be closed by operation of three-way pinch valve 182.
  • Connector tubing 191 extends from first "T” 184 through second pinch valve 192 to second intersection or "T” 190.
  • Other means for controlling fluid flow through tube 191 will be obvious to those skilled in the art and are considered to be within the scope of the present invention.
  • Syringe tubing 199 which is, in turn, connected to syringe pump 198.
  • Syringe pump 198 is of the type that can be controlled to force fluid into or withdraw fluid from syringe tubing 199, and may comprise, for example, a modified Model Baby Bee, manufactured by Bioanalytical Systems, Inc. of West Lafayette, Indiana.
  • syringe pump 198 can be substituted for syringe pump 198 and are considered within the scope of this invention.
  • Other means for moving fluid include but are not limited to a reciprocal piston pump, peristaltic pump, or any other vacuum/pressure source.
  • Reservoir tubing 201 also extends from second "T" 190, goes through third pinch valve 202 and is connected to sterile saline reservoir 200.
  • Sterile saline may be housed within saline reservoir 200.
  • blood is not drawn into reservoir tubing 201; therefore, there is no concern for clotting due to contact of blood in the means for controlling fluid flow through reservoir tubing 201.
  • a wide variety of fluid control means can be used in place of third pinch valve 202. It will be further obvious to those skilled in the art that it is not necessary to have sterile saline reservoir 200 in the apparatus for performing automated micro blood sampling.
  • syringe pump 198 is connected to syringe tubing 199 which is in turn connected to first "T" 184.
  • second "T" 190, connector tubing 191, and third pinch valve 202 are omitted, and second pinch valve 192 may be located so as to control the flow of fluid through syringe tubing 199, or may be omitted.
  • test lead 180 collector tubing 181, connector tubing 191, and first "T" 184
  • an anti-coagulant coating such as CBAS
  • CBAS anti-coagulant coating
  • first and second "T"s 184 and 190 may comprise separate tubing connectors for connection to three tubes.
  • "T" 184 must also include an anti-coagulant coating therein.
  • first and second "T”s 184 and 190 may simply comprise the point at which the tubes are joined by means well known in the art and without the use of a separate connector.
  • Second and third pinch valves 192 and 202 are intended for use with only a single tube - to open or close that tube - and may comprise, for example, Model 161P, manufactured by NR Research of Caldwell, New Jersey.
  • the blood sampling system of Fig. 12 also includes controller 204 for automated control of the system as is described in greater detail herein.
  • Controller 204 which comprises, in this embodiment, a computer and software, is operatively connected, by means well know in the art to: (a) three-way pinch valve 182; (b) second pinch valve 192; (c) third pinch valve 202; (d) syringe pump 198; (e) fraction collector 186; and (f) movement-responsive system 10.
  • controller 204 By the operable connection of controller 204 to movement-responsive system 10, the behavior of animal 12 may be monitored and analyzed, as described earlier herein, and other test leads that may be connected to animal 12 can be controlled.
  • the movement responsive system is independent of controller 204 and uses a separate controller.
  • controller 204 can control the positions of three-way pinch valve 182 to cause the alternate opening and closing of test lead 180 and collector tubing 181; control the open and closed positions of second and third pinch valves 192 and 202, respectively, to cause the opening and closing of connector tubing 191 and reservoir tubing 201, respectively; control syringe pump 198 for forcing fluid into or withdrawing fluid from syringe tubing 199; and control fraction collector 186 to either receive blood samples into the vials 188 or pass fluid coming from collector tubing 181 into drain 189.
  • the present invention may be used to sample body fluids other than blood, either separately or in combination with blood sampling and other biomedical testing.
  • Bile for example, may be sampled using the present invention.
  • Bile salts are added to the wash fluid for replacement of salts removed in the sampling process, thereby avoiding any imbalances due to removal of the bile salts.
  • the combination of bile and blood sampling allows for a complete picture of drug metabolism.
  • Other applications will be obvious to those skilled in the art and are within the scope of the present invention.
  • Fig. 12 is a flow chart of the following operations.
  • the blood sampling system When an operator decides, at step 300, to take one or more blood samples from animal 12, the blood sampling system according to the present invention must first be initialized. As set forth in step 301, initialization of the system is accomplished by filling all tubing with sterile saline and by connecting test lead 180 to animal 12.
  • Test lead 180, collector tubing 181, connector tubing 191, syringe tubing 199, and reservoir tubing 201 are all filled with sterile saline solution residing in reservoir 200 according to the following steps:
  • step 303 To place the withdrawn blood sample volume into fraction collector 186, indicated as step 303, the following steps are then taken:
  • the unused withdrawn blood is then returned to animal 12 in step 304.
  • three-way pinch valve 182 is positioned so that test lead 180 is open and collector tubing 181 is closed.
  • Syringe pump 198 then introduces saline of a volume equal to the volume of blood initially withdrawn from animal 12. This has the effect of returning all unused blood within test lead 180 plus a volume of saline equal to the volume of the blood sample collected to animal 12. In this manner, animal 12 will not become dehydrated as a result of the blood sampling tests performed.
  • Three-way pinch valve 182 is then alternated so that test lead 180 is closed and collector tubing 181 is open.
  • step 305 If, at step 305, it is determined that no additional blood samples are necessary or desired, the method of blood sampling ends at step 306. If, on the other hand, additional blood samples are necessary or desired, in step 307 a flush is performed. Specifically, control fraction collector 186 so that fluid passes to drain 189 and control syringe pump 198 to introduce saline of a volume equal to the volume of the blood sample collected in step 303 plus the volume of connector 184 and collector tubing 181, thereby flushing the part of connector tubing 191 which was exposed to blood in step 302, connector 184, and collector tubing 181.
  • step 308 it is determined whether syringe pump 198 has a sufficient volume of sterile saline available to perform another blood test. If enough saline is available, the method returns to step 302 to withdraw additional blood. If insufficient saline is available, syringe pump 198 is filled with additional saline at step 309.
  • second pinch valve 192 is closed and third pinch valve 202 is opened.
  • Syringe pump 198 then withdraws saline from reservoir 200.
  • third pinch valve 202 is closed and second pinch valve 192 is opened.
  • controller 204 may be controlled by controller 204 to result in an automated blood sampling method. To do so, controller 204 must be able to send control signals to three-way pinch valve 182, second pinch valve 192, third pinch valve 202, syringe pump 198, and fraction collector 186, all of which are operably connected to controller 204. In one embodiment, controller 204 receives a signal from syringe pump 198 indicative of the saline volume in syringe pump 198 to ensure proper volumes of saline are pumped and withdrawn, and/or are available for obtaining the next blood sample.
  • the apparatus also uses non-heparinized sterile saline solution to allow blood serum sampling to be performed on blood samples withdrawn from animal 12. All of these benefits are provided with an apparatus which is inexpensive, easy to setup, and easy to maintain, and with a method that is easy to perform in a time efficient, reliable manner.
  • the movement-responsive system of the present invention provides for the use of continuous leads (tubing, electric lines and optic fibers) without the use of swivels or commutators.
  • This provides for numerous advantages over the prior art including, but not limited to: (a) elimination of the need to compensate for and accommodate the extra system volume of a liquid swivel; (b) no restrictions of the number and type of electrical, fluid or optical leads used in testing; (c) no restrictions on the relative placement of different types of leads; (d) elimination of the need to compensate for the liquid travel time when a swivel is employed; (e) no cross-contamination between channels of a multi-channel liquid swivel; (f) elimination of the potential for cross-talk between electrical or optical channels on a commutator and noise or interference caused by a commutator; (g) avoidance of the extra expense resulting from continual replacement or repair of swivels seals or commutators which experience wear during normal use
  • the present invention provides for tracking and analysis of the rotational and vertical behavior of the animal.
  • Such tracking and/or analysis provides general indicators of the activity of the subject animal and specific indicators of neurochemical or metabolic changes that may be occurring in the animal during testing, and therefore can be very valuable to a researcher.
  • the present invention provides an apparatus whereby no unwanted stress is placed on the test lead.
  • an actual lead is used to move a physical portion of the apparatus which places stress on the lead, and which can harm the animal or result in disconnection of the lead from the animal or to the external device to which the lead is connected.
  • close-ended limit detectors means that counter-rotation of the cage in response to rotation of the animal may be invoked in sufficient time to avoid entanglement, twisting, disconnection or clamping of the leads as results in prior art systems using open-ended sensors which may require one or more revolutions of the animal before reacting with counter-rotation.
  • the present invention provides the researcher with a great deal of flexibility in the types of tests that can be performed with the apparatus.
  • the researcher is not limited to a specific type of lead or leads or a specific number of leads. All this is accomplished with a system which is inexpensive to manufacture, repair and maintain, and which is also highly reliable during operation.
  • the present invention provides the researcher with the added flexibility of performing operant behavior and metabolic testing in a system which is not limited to a specific number or type of leads, and which does not require the use of swivel connecters or commutators.
  • the current invention provides a method and apparatus for automated method for micro sampling of blood which is inexpensive, provides precise sampling capability with a high degree of repeatability, significantly reduces the potential for clotting, allows for blood serum sampling, and is easier to set up and maintain than prior art systems.
  • biomedical test includes, but is not limited to, infusion, electrophysiology blood monitoring, microdialysis, ultrafiltration, electrochemistry, optical fiber transmission, blood sampling, and behavior monitoring. Essentially, it is any test that may be performed on freely-moving animal in a laboratory environment which requires the use of one or more "leads".
  • a “lead” includes fluid tubing, electrical line, optic fiber or other line which is connected to the animal at one end and to an external device at its other end for the purpose of transmission of fluids, light or other stimuli or transmission/receipt of electrical signals, fluids, light transmissions from devices within or on the animal or other data from within or on the animal.
  • the "external device” to which a “lead” is connected at its other end may comprise a source, such as a source of fluid or other stimuli, or a device capable or receiving response signals, fluids, or data from the animal.
  • limit detector means a close-ended sensor which is activated by means such as interruption or reflection of a light beam, magnetic field, radiation field, a flow of air or liquid, or a simple contact with a microswitch, pressure sensitive button, magnet, electrical contact wire, or other mechanism.
  • the "triggering element” may comprise the rotatable element disclosed in the Figures, or any other means of triggering such a limit detector in accordance with the limit detector's activation mechanism and in response to rotational movement of the animal.
  • the angle or spacing between the limit detectors is determined by the angle between or the spacing between (for a non-rotational triggering element) the "primary sensing axis" of the limit detectors, such as the positional axis of optical sensors 70 and 72, as measured in relation to the type of triggering element, i.e., rotational, linear, etc.
  • the limit detectors are in a predetermined relative position with respect to each other.
  • the limit detectors are thus "logically” connected to the rotating means by electrical, physical, magnetic or light contacts to cause activation and deactivation of the rotation of the cage in response to movement (rotational, or otherwise) of the triggering element.

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Claims (43)

  1. Un dispositif permettant de réaliser au moins un test biomédical sur un animal librement en mouvement, comprenant :
    un récipient (14) pour loger l'animal ;
    des moyens (16, 34) pour faire tourner le récipient, les moyens de rotation étant connectés fonctionnellement au récipient ;
    des moyens (32) pour détecter le mouvement de rotation de l'animal, les moyens de détection comprenant :
    des premier et deuxième détecteurs de limite (70, 72) activables, présentant un axe de détection primaire, les premier et deuxième détecteurs de limite étant positionnés de manière que les axes de détection primaire des détecteurs de limite soient situés à une position relative prédéterminée les uns par rapport aux autres, les premier et deuxième détecteurs de limite étant connectés logiquement aux moyens de rotation pour provoquer un mouvement dans le sens des aiguilles d'une montre et dans le sens inverse de celui des aiguilles d'une montre, respectivement, des moyens de rotation, lors de leur activation, et
    un élément de déclenchement (84) déplaçable, dont au moins une partie est prévue pour l'activation et la désactivation des premier et deuxième détecteurs de limite ;
    des moyens (36) pour supporter les moyens de détection au-dessus de l'animal, les moyens de support étant connectés aux moyens de détection ;
    des moyens (26), pour amarrer l'animal aux moyens de détection, les moyens d'amarrage ayant des première et deuxième extrémités, la première extrémité pour la connexion à l'animal, et la deuxième extrémité étant connectée à l'élément de déclenchement des moyens de détection ; et
    de manière que le mouvement de rotation de l'animal provoque le mouvement des moyens d'amarrage, qui, à son tour, provoque le mouvement de l'élément de déclenchement des moyens de détection, et, lors de l'activation soit des premiers, soit des deuxièmes détecteurs de limite, par la partie de l'élément de déclenchement prévue pour l'activation des premiers et des deuxièmes détecteurs de limite, entraîne une contre-rotation du récipient, de par les moyens de rotation, par activation du détecteur de limite correspondant, caractérisé en ce que le récipient comprend une surface inférieure (111) comprenant un trou (110) la traversant, et les moyens de rotation comprennent un trou (123), positionné de manière que, lorsque le récipient est placé sur les moyens de rotation, le trou des moyens de rotation est en alignement avec le trou ménagé dans la surface inférieure du récipient.
  2. Le dispositif selon la revendication 1, comprenant des moyens (116) pour déterminer le comportement opérationnel de l'animal logé à l'intérieur du récipient, les moyens de détermination du comportement opérationnel comprenant des moyens de support (131) pour supporter les moyens de détermination du comportement opérationnel à l'intérieur du récipient, et les moyens de support passant par le trou de la surface inférieure du récipient et le trou des moyens de rotation, lorsque le récipient est placé sur les moyens de rotation.
  3. Le dispositif selon la revendication 2, dans lequel les moyens de détermination du comportement opérationnel comprennent une barre de poussée.
  4. Le dispositif selon la revendication 1, dans lequel le récipient est effilé en direction du haut, depuis la surface inférieure, de manière que de l'urine et des fèces excrétés par l'animal soient amenés, par gravité, vers le trou ménagé dans la surface inférieure du récipient, le dispositif comprenant en outre :
    des moyens, pour séparer les fèces de l'urine, alignés avec le trou ménagé dans la surface inférieure du récipient et le trou des moyens de rotation et proches du trou ménagé dans la surface inférieure du récipient et du trou des moyens de rotation.
  5. Le dispositif selon la revendication 4, comprenant en outre une extension (112) creuse, connectée à la surface inférieure du récipient et alignée avec le trou ménagé dans la surface inférieure du récipient, et dans lequel les moyens séparateurs des fèces et de l'urine comprennent :
    une plaque (120), ayant une surface inférieure et une surface supérieure, la plaque ayant au moins un trou (124) la traversant, dimensionné de manière que l'urine passe mais que les fèces ne passent pas à travers lui ;
    un arbre (126) creux, fixé à la surface inférieure de la plaque ; et
    un entonnoir (132) creux, comprenant une partie formant goulot et une partie évasée, la partie formant goulot étant dimensionnée de manière qu'elle puisse être fixée à l'arbre creux attaché à la surface inférieure de la plaque,
    de manière que, lorsque la partie formant goulot de l'entonnoir est attachée à l'arbre creux, l'urine puisse s'écouler à travers la au moins une ouverture ménagée dans la plaque, entre l'extension creuse et l'arbre creux, et soit guidée vers le bas par la partie flasquée de l'entonnoir, et de manière que les fèces puissent tomber à travers le au moins un trou ménagé dans la plaque, en passant à travers l'arbre creux.
  6. Le dispositif selon la revendication 5, comprenant en outre :
    des moyens collecteurs (134), pour collecter les fluides, les moyens collecteurs comprenant une surface inférieure, une paroi extérieure (142) et une paroi intérieure (138), les moyens collecteurs situés sur la paroi extérieure étant plus grands que la partie évasée de l'entonnoir et plus grands que l'extension creuse, les moyens collecteurs situés sur la paroi intérieure étant plus petits que la partie évasée de l'entonnoir et pas plus grands que l'arbre creux, les moyens collecteurs étant alignés avec l'arbre creux et proches de la partie évasée de l'entonnoir, les moyens collecteurs étant situés sous l'arbre creux et sous la partie évasée de l'entonnoir,
    de manière que de l'urine, guidée par la partie évasée de l'entonnoir, tombe dans les moyens collecteurs, entre la paroi intérieure et celle extérieure, et de manière que les fèces tombant par l'arbre creux tombent dans les moyens collecteurs, dans la paroi intérieure.
  7. Le dispositif selon la revendication 4, comprenant en outre une extension (112) creuse, connectée à la surface inférieure du récipient et alignée avec le trou ménagé dans la surface inférieure du récipient, et dans lequel les moyens (146) de séparation des fèces et de l'urine comprennent :
    une section effilée (150), une bordure inférieure (152) et un sommet (156), la bordure inférieure des moyens séparateurs étant plus grande que l'extension creuse, les moyens séparateurs étant perméables et dimensionnés pour permettre à l'urine de passer à travers ces moyens, mais pour empêcher les fèces de passer par les moyens séparateurs.
  8. Le dispositif selon la revendication 7, comprenant en outre des moyens collecteurs d'urine (144), comprenant une surface inférieure et au moins une paroi (149), les moyens collecteurs d'urine étant plus grands que l'extension creuse et pas plus grands que les moyens séparateurs, les moyens collecteurs étant alignés avec les moyens séparateurs et placés au-dessous des moyens séparateurs.
  9. Le dispositif selon la revendication 8, dans lequel la au moins une paroi des moyens collecteurs d'urine comprend une bordure supérieure (158), et dans lequel les moyens séparateurs sont situés à l'intérieur des moyens collecteurs d'urine, comprenant en outre :
    des moyens (154), pour supporter les moyens séparateurs, de manière que le sommet des moyens séparateurs soit maintenu en une position inférieure à la bordure supérieure de la paroi des moyens collecteurs d'urine, et de manière que la bordure inférieure des moyens séparateurs soit située au-dessus de la surface inférieure des moyens collecteurs.
  10. Le dispositif selon la revendication 9, dans lequel les moyens pour supporter les moyens séparateurs comprennent la bordure inférieure (152) des moyens séparateurs, dimensionnée pour établir un contact de friction avec la paroi des moyens collecteurs d'urine.
  11. Dispositif selon la revendication 7, comprenant en outre des moyens collecteurs de fèces (167), pour recevoir des fèces, positionnés à proximité des moyens séparateurs, de manière que les fèces tombant sur les moyens séparateurs soient dirigés sur les moyens collecteurs de fèces.
  12. Le dispositif selon la revendication 11, dans lequel les moyens séparateurs comprennent en outre une partie verticale (154) entourant la bordure inférieure et s'étendant vers le haut, à partir de la bordure inférieure, et dans lequel les moyens collecteurs de fèces comprennent :
    un drain (167), formé par la partie verticale de l'insert et la section effilée de l'insert.
  13. Le dispositif selon la revendication 1, comprenant en outre :
    des moyens (160), pour supporter l'animal au dessus de la surface inférieure du récipient.
  14. Le dispositif selon la revendication 13, dans lequel les moyens pour supporter l'animal comprennent une pluralité d'organes se chevauchant.
  15. Le dispositif selon la revendication 13, dans lequel les moyens pour supporter l'animal comprennent une pluralité d'organes sensiblement parallèles.
  16. Le dispositif selon la revendication 1, comprenant en outre :
    des moyens d'appréhension verticale (101), pour appréhender un mouvement vertical de l'animal, incluant un élément d'activation (38) qui se déplace en réponse à un mouvement vertical de l'animal, et un élément de détection verticale (102), positionné pour détecter le mouvement de l'élément d'activation et fournissant, à partir de celui-ci, un signal de sortie tel que le mouvement vertical de l'animal provoque la détection du mouvement par l'élément de détection verticale et l'activation de l'élément d'activation.
  17. Le dispositif selon la revendication 16, dans lequel l'élément de détection des moyens d'appréhension verticale comprend un capteur optique (102), activé lors de l'interruption d'un faisceau lumineux émanant de celui-ci.
  18. Le dispositif selon la revendication 16, comprenant en outre un bras équilibré (38), pour une connexion fonctionnelle à l'animal, à l'aide des moyens d'amarrage, et dans lequel le bras équilibré comprend l'élément d'activation des moyens d'appréhension verticale.
  19. Le dispositif selon la revendication 16, comprenant en outre :
    des moyens pour analyser le mouvement vertical de l'animal (108), connectés fonctionnellement au signal de sortie de l'élément de détection verticale.
  20. Le dispositif selon la revendication 19, dans lequel les moyens d'analyse comprennent une entrée, réagissant au signal de sortie de l'élément de détection verticale, et dans lequel les moyens d'analyse comprennent en outre des moyens de positionnement temporel, connectés fonctionnellement à l'entrée pour associer le temps au signal de sortie de l'élément de détection verticale, de manière que les moyens d'analyse fournissent un historique temporel du mouvement vertical de l'animal.
  21. Le dispositif selon la revendication 19, dans lequel les moyens d'analyse comprennent un enregistreur de graphiques à bande.
  22. Le dispositif selon la revendication 19, dans lequel les moyens d'analyse comprennent un processeur de données.
  23. Le dispositif selon la revendication 19, dans lequel les moyens d'amarrage comprennent des premiers moyens (135), pour guider un fluide, et comprenant en outre :
    un dispositif de test externe, comprenant :
    des deuxièmes moyens pour guider un fluide, incluant un premier (180), un deuxième (181) et un troisième (191) tube, connectés fonctionnellement les uns aux autres, le premier tube étant connecté fonctionnellement aux moyens d'amarrage ;
    des moyens (186), pour recevoir du fluide, connectés fonctionnellement au deuxième tube ;
    des moyens (198), pour pomper du fluide, connectés fonctionnellement au troisième tube ; et
    des premiers et deuxièmes moyens de commande de fluide (182), chacun des premiers et deuxièmes moyens de commande de fluide ayant une position ouverte et une position fermée, chacun des premiers et deuxièmes moyens de commande de fluide étant connecté fonctionnellement au premier et au deuxième tube, respectivement, de manière que, lorsque chacun des premiers et deuxièmes moyens de commande de fluide est ouvert, du fluide est libre de s'écouler à travers le tube correspondant, et, lorsque chacun des premiers et deuxièmes moyens de commande de fluide est fermé, un fluide est empêché de s'écouler à travers le tube correspondant.
  24. Le dispositif selon la revendication 19, comprenant en outre :
    des moyens de commande de collecte d'échantillon (204), pour commander un écoulement de fluide, sont connectés fonctionnellement aux moyens de pompage de fluide, et aux premiers et deuxième moyens de commande de fluide.
  25. Le dispositif selon la revendication 24, comprenant en outre le fait que les moyens de commande de collecte d'échantillon sont connectés fonctionnellement aux moyens de réception de fluide.
  26. Le dispositif selon la revendication 23, dans lequel chacun des premiers et deuxième moyens de commande de fluide comprend une soupape à pincement.
  27. Le dispositif selon la revendication 26, dans lequel les première et deuxième soupapes à pincement composent, conjointement, une soupape à pincement à trois voies (182), ayant une première et une deuxième position, telles que, dans la première position, le premier tube soit fermé et que le deuxième tube soit ouvert et que, dans la deuxième position, le premier tube soit ouvert et le deuxième tube soit fermé.
  28. Le dispositif selon la revendication 23, caractérisé en ce que les moyens de pompage du fluide comprennent au moins une pompe de seringue (198).
  29. Le dispositif selon la revendication 24, caractérisé en ce que les moyens de commande de collecte d'échantillon comprennent un ordinateur personnel.
  30. Un procédé pour effectuer un micro-échantillonnage de fluide automatisé, comprenant les étapes consistant à :
    fournir le dispositif selon la revendication 23, dans lequel les premier (180), deuxième (181), et troisième (191) tubes sont remplis d'une solution, et dans lequel les premiers moyens de commande de fluide sont fermés, et les deuxièmes moyens de commande de fluide sont ouverts ;
    pousser la solution dans le troisième tube, en utilisant les moyens (198) pour déplacer le fluide, de manière à rincer le deuxième tube avec la solution ;
    fermer les deuxièmes moyens de commande de fluide et ouvrir les premiers moyens de commande de fluide ;
    extraire la solution hors du troisième tube, avec les moyens de pompage de fluide, de manière à extraire de l'animal une quantité discrète de fluide, suffisante pour remplir les moyens d'amarrage (135) et le premier tube avec du fluide et pour remplir le troisième tube avec l'échantillon de fluide souhaité ;
    ouvrir les deuxièmes moyens de commande de fluide et fermer les premiers moyens de commande de fluide ;
    pousser dans le troisième tube, à l'aide des moyens de pompage de fluide, un volume de solution égal au volume du deuxième tube, de manière à forcer l'échantillon de fluide à aller vers l'extrémité du deuxième tube ;
    à partir des moyens de pompage de fluide, pousser dans le troisième tube une quantité de solution égale au volume de l'échantillon de fluide, de manière à déposer l'échantillon de fluide dans les moyens (186) de réception de fluide ;
    fermer les deuxièmes moyens de commande de fluide et ouvrir les premiers moyens de commande de fluide ;
    à partir des moyens de commande de fluide, pousser dans le troisième tube suffisamment de solution, de manière à forcer le fluide se trouvant dans le premier tube et les moyens d'amarrage à revenir dans l'animal, ainsi qu'une quantité de solution égale au volume de l'échantillon de fluide extrait.
  31. Le procédé pour effectuer un micro-échantillonnage de fluide automatisé selon la revendication 30, prévoyant en outre des moyens (200) pour fournir une solution, et fournissant un quatrième tube (201), connectant fonctionnellement les moyens de fourniture de solution et les moyens de pompage de fluide, de manière que les moyens de fourniture de solution soient en communication avec les moyens de pompage de fluide ; et
    fourniture de troisièmes (192) et de quatrièmes (202) moyens de commande de fluide, chacun ayant une position fermée et une position ouverte, connectés fonctionnellement au troisième et au quatrième tube, respectivement, de manière que, lorsque les troisièmes ou quatrièmes moyens de commande de fluide se trouvent à la position fermée, l'écoulement de fluide dans le tube correspondant soit restreint et lorsque les troisièmes ou quatrièmes moyens de commande de fluide se trouvent à la position ouverte, l'écoulement de fluide dans le tube correspondant soit libre,
    l'invention comprenant les étapes consistant à :
    ouvrir les troisièmes moyens de commande de fluide, et fermer les quatrièmes moyens de commande de fluide,
    extraire de la solution des moyens de fourniture de solution, avec les moyens de pompage de fluide, de manière à recharger les moyens de pompage de fluide avec de la solution ;
    fermer les quatrièmes moyens de commande de fluide, et
    ouvrir les troisièmes moyens de commande de fluide.
  32. Le procédé pour effectuer un micro-échantillonnage de fluide automatisé selon la revendication 30, comprenant en outre, avant l'étape de poussée de solution dans le troisième tube, les étapes consistant à :
    fournir des moyens de commande de sélection d'échantillon (204), pour commander l'écoulement de fluide, les moyens de commande de collecte d'échantillon étant connectés fonctionnellement aux moyens (198) de pompage de fluide, et aux premiers et deuxièmes moyens de commande (182) ; et activer les moyens de commande de collecte d'échantillon, de manière que les étapes subséquentes soient commandées par les moyens de commande de collecte d'échantillon.
  33. Le procédé pour effectuer un micro-échantillonnage de fluide automatisé selon la revendication 32, dans lequel le dispositif comprend en outre les moyens de commande de collecte d'échantillon, connectés fonctionnellement aux moyens (186) de réception de fluide, comprenant en outre, après l'étape de poussée dans le troisième tube, avec les moyens de pompage de fluide, d'un volume de solution égal au volume du deuxième tube, de manière à forcer le deuxième échantillon à aller vers l'extrémité du deuxième tube, l'étape consistant à :
    positionner les moyens de réception de fluide de manière à collecter l'échantillon de fluide.
  34. Le dispositif selon la revendication 23, dans lequel chacun, des premier, deuxième et troisième tubes, est revêtu sur sa surface intérieure d'un anticoagulant.
  35. Le dispositif selon la revendication 1, comprenant en outre :
    des moyens pour guider un fluide, incluant un premier (180), un deuxième (181) et un troisième (191) tube, connectés fonctionnellement les uns aux autres, le premier tube étant susceptible d'être connecté fonctionnellement à l'animal ;
    des moyens (186), pour recevoir du fluide, connectés fonctionnellement au deuxième tube ;
    des moyens (198), pour pomper du fluide, connectés fonctionnellement au troisième tube ; et
    des premiers et deuxièmes moyens de commande de fluide (182), chacun des premiers et deuxièmes moyens de commande de fluide ayant une position ouverte et une position fermée, chacun des premiers et deuxièmes moyens de commande de fluide étant connecté fonctionnellement au premier et au deuxième tube, respectivement, de manière que, lorsque chacun des premiers et deuxièmes moyens de commande de fluide est ouvert, du fluide est libre de s'écouler à travers le tube correspondant, et, lorsque chacun des premiers et deuxièmes moyens de commande de fluide est fermé, un fluide est empêché de s'écouler à travers le tube correspondant.
  36. Le dispositif selon la revendication 35, comprenant en outre :
    des moyens de commande de collecte d'échantillon (204), pour commander un écoulement de fluide, connectés fonctionnellement aux moyens de pompage de fluide, et aux premiers et deuxièmes moyens de commande de fluide.
  37. Le dispositif selon la revendication 36, dans lequel les moyens de commande de collecte d'échantillon sont connectés fonctionnellement aux moyens de réception de fluide.
  38. Le dispositif selon la revendication 35, dans lequel chacun des premiers et deuxième moyens de commande de fluide comprend une soupape à pincement.
  39. Le dispositif selon la revendication 38, dans lequel les première et deuxième soupapes à pincement composent, conjointement, une soupape à pincement à trois voies (182), ayant une première et une deuxième position, telles que, dans la première position, le premier tube soit fermé et que le deuxième tube soit ouvert et que, dans la deuxième position, le premier tube soit ouvert et le deuxième tube soit fermé.
  40. Le dispositif selon la revendication 35, dans lequel les moyens de pompage du fluide comprennent au moins une pompe de seringue (198).
  41. Le dispositif selon la revendication 36, dans lequel les moyens de commande de collecte d'échantillon comprennent un ordinateur personnel.
  42. Le procédé pour effectuer un micro-échantillonnage de fluide automatisé selon la revendication 32, dans lequel le dispositif comprend en outre les moyens de commande de collecte d'échantillon, connectés fonctionnellement aux moyens de réception de fluide, comprenant en outre, après l'étape de poussée dans le troisième tube, avec les moyens de pompage de fluide, d'un volume de solution égal au volume du deuxième tube, de manière à forcer le deuxième échantillon à aller vers l'extrémité du deuxième tube, l'étape consistant à :
    positionner les moyens de réception de fluide de manière à collecter l'échantillon de fluide.
  43. Le dispositif selon la revendication 42, dans lequel chacun, des premier, deuxième et troisième tubes, est revêtu sur sa surface intérieure d'un anticoagulant.
EP99307384A 1998-09-18 1999-09-17 Dispositif capteur de mouvement permettant de réaliser des tests sur des animaux librement en mouvement Expired - Lifetime EP0986951B1 (fr)

Applications Claiming Priority (2)

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US09/156,459 US6062224A (en) 1997-04-17 1998-09-18 Movement-response system for conducting tests on freely-moving animals
US156459 1998-09-18

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EP0986951A2 EP0986951A2 (fr) 2000-03-22
EP0986951A3 EP0986951A3 (fr) 2001-06-27
EP0986951B1 true EP0986951B1 (fr) 2008-09-03

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ATE406794T1 (de) 2008-09-15
US6062224A (en) 2000-05-16
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DE69939446D1 (de) 2008-10-16
EP0986951A3 (fr) 2001-06-27

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